Effect of thrombin in the injury, especially on chemotaxis and accumulation of the inflammatory cells

凝血酶是丝氨酸蛋白酶家族的一员，在凝血、炎症、调节血管和中枢神经系统（CNS）等方面具有多种功能。凝血酶在脑组织损伤恢复中发挥作用的同时，也通过神经胶质反应和损伤后瘢痕形成引起脑后损伤。为了阐明凝血酶对治疗应用目的的影响，我们在大鼠脑损伤模型中使用抗凝血酶药物阿加曲班进行组织学研究：(1)凝血酶对炎症细胞的作用：通过在内皮细胞上表达黏附分子使炎症细胞浸润和积聚，特别是在小血管周围；(2)凝血酶对中枢神经系统细胞的作用：在大鼠脑损伤模型中，当给予过量凝血酶或凝血酶抑制剂时，胶质细胞的反应，特别是星形胶质细胞。结果：凝血酶抑制剂能抑制炎症细胞的浸润和以vimentin阳性星形胶质细胞为主的过度胶质增生，但对gfap阳性星形胶质细胞沿损伤区表达无影响。结果2：凝血酶加速了脑缺损边缘内皮细胞炎症细胞的浸润及e -选择素、ICAM-1的表达。结果3：凝血酶抑制剂抑制炎症细胞的浸润和内皮细胞上ICAM-1的表达，抑制Mac-1阳性细胞沿脑缺损边缘的积累。结论凝血酶通过在内皮细胞上表达粘附分子引起炎症细胞浸润，导致急性炎症后继发性脑损伤。凝血酶加速脑损伤后静脉蛋白阳性星形胶质细胞的增殖。凝血酶抑制剂可减轻继发性脑损伤，促进神经再生。少

Thrombin is a member of serine protease family, and has been well known to have multifunctions in coagulation, inflammation, regulation of blood vessels and central nervous systems (CNS). While thrombin effects on the brain tissues in restoring from damage, it also causes the post brain damage through glial reaction and scar formation after injury.In order to elucidate the effects of thrombin on the purpose of therapeutic application, we investigated the following studies by using anti-thrombin drug, named argatroban, in a rat brain injury model, histologically :(1) Effect of thrombin on the inflammatory cells : infiltration and accumulation of inflammatory cells, especially around the small vessels through expressing the adhesion molecules on the endothelial cells, and(2) Effects of thrombin on cells comprising central nervous system : glial response, especially, of the astrocytes when excess of thrombin or inhibitor for thrombin were administered in a rat brain injury model.Result 1 … More : Thrombin inhibitor suppressed the infiltration of inflammatory cells and excessive gliosis mainly composed of vimentin-positive astroglia, but not effected on the expression of GFAP-positive astrocytes along the injured area of rat brain.Result 2 : Thrombin accelerated the infiltration of inflammatory cells and the expression of E-selectin and ICAM-1 on the endothelial cells along the edge of brain defect.Result 3 : Thrombin inhibitor suppressed the infiltration of inflammatory cells and the expression of ICAM-1 on the endothelial cells, and also suppressed the accumulation of Mac-1 positive cell along the edge of brain defect.ConclusionThrombin caused infiltration of inflammatory cells through the expression of adhesion molecules on the endothelial cells, and led to secondary brain damage after acute inflammation.Thrombin accelerated proliferation of vimentin-positive astrocytes after brain injury.Thrombin inhibitor may minimize the secondary brain damage, and promote the neural regeneration. Less